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Abstract Compounds that can induce oxidative stress in cancer cells while remaining nontoxic to healthy cells are extremely promising for potential anticancer drugs. 2,2′:6′,2′′-terpyridine-metal complexes possess these properties. The high level of activity (IC50 = 0.605 µM) of 2,2′:6′,2′′-terpyridine-metal complexes on lung, breast, pancreatic, and glioblastoma multiforme cancer lines and their selectivity (SI > 41.32) on human normal fibroblasts were confirmed and presented in this paper. The mechanism of action of these compounds is associated with the generation of reactive oxygen species, which affects several cellular pathways and signals. The results demonstrate that 2,2′:6′,2′′-terpyridine-metal complexes affect cell cycle inhibition in the G0/G1 phase as well as the activation of apoptosis and autophagy cell death. These results were confirmed in several independent studies, including experiments measuring the fluorescence levels of reactive oxygen species, flow cytometry, and gene and protein analysis.

Abstract Rhegmatogenous retinal detachment (RRD) is a sight-threatening condition with rising global incidence. Identifying factors contributing to seasonal variations in RRD would allow a better understanding of RRD pathophysiology. We therefore performed a retrospective case series study investigating the relationship between RRD occurrence and meteorological factors throughout metropolitan France (the METEO-POC study), particularly the mean temperature over the preceding 10-day period (T-1). Adult patients having undergone RRD surgery and residing in one of the three most populated urban areas of each French region were included (January 2011–December 2018). The study involved 21,166 patients with idiopathic RRD (61.1% males, mean age 59.8–65.1 years). RRD incidence per 100,000 inhabitants increased from 7.79 to 11.81. RRD occurrence was not significantly associated with mean temperature over T-1 in the majority of urban areas (31/36). In a minority of areas (5/36) we observed correlations between RRD incidence and mean temperature over T-1, however these were extremely weak (r = 0.1–0.2; p

Patellar dislocations are common injuries that can lead to recurrent dislocations and instability. Patellar instability is a complex problem and requires a multifactorial approach. Over the years, many different repair and reconstruction techniques has been developed. The variety of techniques proves that there is no best procedure, and different options must be taken into consideration in every case. Many of these techniques are complicated and require graft harvesting or drilling through the patella. We present a technique of arthroscopic patellar stabilization with a single suture anchor and lateral release that is easy to perform, cost-effective, and does not require drilling tunnels through patella or graft harvesting.

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To functionalize the NiTi alloy, multifunctional innovative nanocoatings of Ag-TiO2 and Ag-TiO2 doped with hydroxyapatite were engineered on its surface. The coatings were thoroughly characterized, focusing on surface topography and key functional properties, including adhesion, surface wettability, biocompatibility, antibacterial activity, and corrosion resistance. The electrochemical corrosion kinetics in a simulated body fluid and the mechanisms were analyzed. The coatings exhibited hydrophilic properties and were biocompatible with fibroblast and osteoblast cells while also demonstrating antibacterial activity against E. coli and S. epidermidis. The coatings adhered strongly to the NiTi substrate, with superior adhesion observed in the hydroxyapatite-doped layers. Conversely, the Ag-TiO2 layers showed enhanced corrosion resistance.

Objectives CpG ODN is a Toll-like receptor 9 agonist with immunotherapeutic potential for many cancer types, including aggressive breast cancers. There is strong interest in utilizing CpG ODN as an adjuvant to improve clinical efficacy of current treatments and immunogenicity of breast cancers not traditionally responsive to active immunotherapy, such as those that are human epidermal growth factor receptor 2 (HER2)-positive. This study aimed to study the efficacy and safety of combination CpG ODN plus anti-HER2 antibody trastuzumab treatment in patients with advanced/metastatic breast cancer. Methods This single-arm, open-label phase II clinical trial treated patients (n = 6) with advanced/metastatic HER2-positive breast cancer with weekly subcutaneous CpG ODN and trastuzumab. Patients may have received any number of prior therapies to be enrolled (most enrolled at median 1 prior line of chemotherapy). Peripheral blood was collected at baseline and weeks 2, 6, 12, and 18 for immune analyses. Six patients were enrolled and 50% achieved stable disease (SD) response. Results Median PFS was 8.3 months. Three of the six patients enrolled opted to stop treatment due to tolerability issues. Multiplex assay for cytokine measurements revealed significantly higher VEGF-D levels at week 2 compared to baseline. Peripheral blood mononuclear cells analyzed by flow cytometry showed a significant increase in monocytic MDSC between weeks 6 and 12. Patients with progressive disease tended to have higher levels of week 6 monocytic MDSC and PD-1+ T cells than patients with SD. NK cell populations did not significantly change throughout treatment. Conclusions CpG ODN and trastuzumab treatment of metastatic HER2 + breast cancer was safe but was not tolerable for all patients. This combination did induce potentially predictive immune profile changes in treated patients with metastatic HER2 + breast cancer, the significance of which needs to be further explored.

Two new species and two new subspecies of the satyrine butterfly genus Punargentus Heimlich, P. atusparia sp. n., P. heimlichi sp. n., P. blanchardi libertas ssp. n. and P. atusparia yupania ssp. n., are described from north-central Peru (Ancash, Huánuco and La Libertad). The affinities of the new taxa are evaluated based on molecular data obtained using target enrichment and COI barcoding. Punargentus is fully supported and consists of two branches, the P. lamna clade with four species and P. blanchardi clade with three species, two of which are described here. Species in the P. blanchardi clade occur in Andean shrubland, at altitudes between 2800-3600 m, whereas those in the P. lamna clade occur in puna grassland at 3600-4600 m, with occasional overlaps. Based on their habitat preferences, none of the newly described species are in need of immediate conservation measures. The genus Etcheverrius Herrera is reinstated, with E. chiliensis (Guérin-Méneville) and E. tandilensis (Köhler), comb. n.

Abstract Quantum information processing promises to revolutionise computing; quantum algorithms have been discovered that address common tasks significantly more efficiently than their classical counterparts. For a physical system to be a viable quantum computer it must be possible to initialise its quantum state, to realise a set of universal quantum logic gates, including at least one multi-qubit gate, and to make measurements of qubit states. Molecular Electron Spin Qubits (MESQs) have been proposed to fulfil these criteria, as their bottom-up synthesis should facilitate tuning properties as desired and the reproducible production of multi-MESQ structures. Here we explore how to perform a two-qubit entangling gate on a multi-MESQ system, and how to readout the state via quantum state tomography. We propose methods of accomplishing both procedures using multifrequency pulse Electron Paramagnetic Resonance (EPR) and apply them to a model MESQ structure consisting of two nitroxide spin centres. Our results confirm the methodological principles and shed light on the experimental hurdles which must be overcome to realise a demonstration of controlled entanglement on this system.

The paper aims to identify how Industry 4.0 technologies affect the quality and speed of the managers’ decision-making process across the different stages of the value chain, based on the example of the manufacturing sector. The paper adopts qualitative research, based on nine in-depth interviews with key informants, to capture senior executives’ experiences with implementing Industry 4.0 technologies in their organisations. The research is focused on three manufacturing industries: the automotive, food and furniture industries. The research shows that depending on the stage of the value chain, different Industry 4.0 technologies are more suitable for the support of managers’ decisions. Various Industry 4.0 technologies support decision-making at different stages of the manufacturing value chain. In the Design stage, 3D printing and scanning technologies play a crucial role. In the case of Inbound Logistics, robotisation, automation, Big Data analysis, and Business Intelligence are most useful. During the Manufacturing stage, robotisation, automation, 3D printing, scanning, Business Intelligence, cloud computing, and machine-to-machine (M2M) integration enable quick decision-making and speed up production. Sensors and the Internet of Things (IoT) optimise distribution in the Outbound Logistics stage. And finally, Business Intelligence supports decisions within the Sales and Marketing stage. It is also the most versatile technology among all particular stages. The paper provides empirical evidence on the Industry 4.0 technology support in decision-making at different stages of the manufacturing value chain, which leads to more effective value chain management, ensuring faster and more accurate decisions at each value-chain stage. When using properly selected Industry 4.0 technologies, managers can optimise their production processes, reduce costs, avoid errors and improve customer satisfaction. Simultaneously, Industry 4.0 technologies facilitate predictive analytics to forecast and anticipate future demand, quality issues, and potential risks. This knowledge allows organisations to make better decisions and take proactive actions to prevent problems.

Medical support in crisis situations is a major challenge. Efficient implementation of the medical evacuation process especially in operations with limited human resources that may occur during armed conflicts can limit the loss of these resources. Proper evacuation of wounded soldiers from the battlefield can increase the chances of their survival and rapid return to further military operations. This paper presents the technical details of the decision support system for medical evacuation to support this process. The basis for the functioning of this system is the continuous measurement of vital signs of soldiers via a specialized measurement module with a set of medical sensors. Vital signs values are then transmitted via the communication module to the analysis and inference module, which automatically determines the color of medical triage and the soldier’s chance of survival. This paper presents the results of tests of our system to validate it, which were carried out using test vectors of soldiers’ vital signs, as well as the results of the system’s performance on a group of volunteers who performed typical activities of tactical operations. The results of this study showed the usefulness of the developed system for supporting military medical services in military operations.

Detecting instruments in a music signal is often used in database indexing, song annotation, and creating applications for musicians and music producers. Therefore, effective methods that automatically solve this issue need to be created. In this paper, the mentioned task is solved using mel-frequency cepstral coefficients (MFCC) and various architectures of artificial neural networks. The authors’ contribution to the development of automatic instrument detection covers the methods used, particularly the neural network architectures and the voting committees created. All these methods were evaluated, and the results are presented and discussed in the paper. The proposed automatic instrument detection methods show that the best classification quality was obtained for an extensive model, which is the so-called committee of voting classifiers.

Katarzyna Malarz,1,* Julia Korzuch,2,* Tainah Dorina Marforio,3 Katarzyna Balin,1 Matteo Calvaresi,3 Anna Mrozek-Wilczkiewicz,1 Robert Musiol,2 Maciej Serda2 1A. Chełkowski Institute of Physics, University of Silesia in Katowice, Chorzów, Poland; 2Institute of Chemistry, University of Silesia in Katowice, Katowice, Poland; 3Department of Chemistry “Giacomo Ciamician”, University of Bologna, Bologna, Italy*These authors contributed equally to this workCorrespondence: Maciej Serda; Katarzyna Malarz, Email maciej.serda@us.edu.pl; katarzyna.malarz@us.edu.plIntroduction: Thanks to recent advances in synthetic methodology, water-soluble fullerene nanomaterials that interfere with biomolecules, especially DNA/RNA and selected proteins, have been found with tremendous potential for applications in nanomedicine. Herein, we describe the synthesis and evaluation of a water-soluble glycine-derived [60]fullerene hexakisadduct (HDGF) with Th symmetry, which is a first-in-class BTK protein inhibitor.Methods: We synthesized and characterized glycine derived [60]fullerene using NMR, ESI-MS, and ATR-FT-IR. DLS and zeta potential were measured and high-resolution transmission electron microscopy (HRTEM) observations were performed. The chemical composition of the water-soluble fullerene nanomaterial was examined by X-ray photoelectron spectrometry. To observe aggregate formation, the cryo-TEM analysis was carried out. The docking studies and molecular dynamic simulations were performed to determine interactions between HDGF and BTK. The in vitro cytotoxicity was evaluated on RAJI and K562 blood cancer cell lines. Subsequently, we examined the induction of cell death by autophagy and apoptosis by determining the expression levels of crucial genes and caspases. We investigated the direct association of HDGF on inhibition of the BTK signalling pathway by examining changes in the calcium levels in RAJI cells after treatment. The inhibitory potential of HDGF against non-receptor tyrosine kinases was evaluated. Finally, we assessed the effects of HDGF and ibrutinib on the expression of the BTK protein and downstream signal transduction in RAJI cells following anti-IgM stimulation.Results: Computational studies revealed that the inhibitory activity of the obtained [60]fullerene derivative is multifaceted: it hampers the BTK active site, interacting directly with the catalytic residues, rendering it inaccessible to phosphorylation, and binds to residues that form the ATP binding pocket. The anticancer activity of produced carbon nanomaterial revealed that it inhibited the BTK protein and its downstream pathways, including PLC and Akt proteins, at the cellular level. The mechanistic studies suggested the formation of autophagosomes (increased gene expression of LC3 and p62) and two caspases (caspase-3 and − 9) were responsible for the activation and progression of apoptosis.Conclusion: These data illustrate the potential of fullerene-based BTK protein inhibitors as nanotherapeutics for blood cancer and provide helpful information to support the future development of fullerene nanomaterials as a novel class of enzyme inhibitors.Graphical Abstract: Keywords: fullerenes, BTK inhibitor, anticancer agent, autophagy, apoptosis

Among many important functions, bees play a key role in food production. Unfortunately, worldwide bee populations have been decreasing since 2007. One reason for the decrease of adult worker bees is varroosis, a parasitic disease caused by the Varroa destructor (V. destructor) mite. Varroosis can be quickly eliminated from beehives once detected. However, this requires them to be monitored continuously during periods of bee activity to ensure that V. destructor mites are detected before they spread and infest the entire beehive. To this end, the use of Internet of things (IoT) devices can significantly increase detection speed. Comprehensive solutions are required that can cover entire apiaries and prevent the disease from spreading between hives and apiaries. In this paper, we present a solution for global monitoring of apiaries and the detection of V. destructor mites in beehives. Our solution captures and processes video streams from camera-based IoT devices, analyzes those streams using edge computing, and constructs a global collection of cases within the cloud. We have designed an IoT device that monitors bees and detects V. destructor infestation via video stream analysis on a GPU-accelerated Nvidia Jetson Nano. Experimental results show that the detection process can be run in real time while maintaining similar efficacy to alternative approaches.

The demand for digitizing manufacturing and controlling processes has been steadily increasing in recent years. Digitization relies on different techniques and equipment, which produces various data types and further influences the process of space understanding and area recognition. This paper provides an updated view of these data structures and high-level categories of techniques and methods leading to indoor environment segmentation and the discovery of its semantic meaning. To achieve this, we followed the Systematic Literature Review (SLR) methodology and covered a wide range of solutions, from floor plan understanding through 3D model reconstruction and scene recognition to indoor navigation. Based on the obtained SLR results, we identified three different taxonomies (the taxonomy of underlying data type, of performed analysis process, and of accomplished task), which constitute different perspectives we can adopt to study the existing works in the field of space understanding. Our investigations clearly show that the progress of works in this field is accelerating, leading to more sophisticated techniques that rely on multidimensional structures and complex representations, while the processing itself has become focused on artificial intelligence-based methods.

In this study, a series of four surface-active compounds—N-alkyl betaine ethyl ester chlorides, CnBetC2Cl—were synthesized and characterized in aqueous solutions. As with other alkyl betaines, these amphiphiles can be practically used, for example, as co-surfactants and/or solubility enhancers acting according to hydrotropic or micellar mechanisms, depending on the alkyl chain length in the amine. We focused on the representatives of the medium alkyl chain length (C6–C12) to find the dependence between the alkyl chain length in N-alkyl betaine ethyl ester chlorides and the surface, volumetric, acoustic, and viscometric properties of their solutions. Ethyl esters, the derivatives of amino acids, were chosen to increase functionality and take advantage of possible hydrolysis in solutions at higher pH, which is also a key parameter in biodegradability. The micellization parameters were calculated based on the physicochemical characteristics. We focused our interest on the ester with a dodecyl substituent since we can compare and discuss its properties with some other C12 representatives that are available in literature. Surprisingly, its micellization characteristic is almost temperature-independent in the investigated temperature range, t = (15–45) °C. Particularly interesting are the results of dynamic light scattering (DLS), which show that the changes in physicochemical parameters of the C12 homolog around the CMC are caused by the two types of micelles of different sizes present in solutions.

This paper addresses the problem of describing the complex linked coupling faults of memory devices and formulating the necessary and sufficient conditions for their detection. The main contribution of the proposed approach is based on using a new formal model of such faults, the critical element of which is the introduction of roles and scenarios performed by the cells involved in the fault. Three roles are defined such that the cells of the complex linked coupling faults perform, namely, the roles of the aggressor (A), the victim (V), and both (B), performed by two cells simultaneously in relation to each other. The memory march test and applied address sequence and background determine the scenario for implementing the roles of memory faulty cells. The necessary and sufficient conditions for detecting linked coupling faults are given based on a new formal model. Formally, the undetectable linked coupling faults are defined, and the conditions for their detection are formulated using multirun memory march tests. The experimental investigation confirmed the validity of the proposed formulated statements. Based on the example of a linked coupling fault, this study demonstrates the fulfillment of the necessary and sufficient conditions for its detection using a single march test. As demonstrated in this article, employing the approach proposed by the authors, a two-pass march C test, for instance, enables the attainment of 55.42% fault coverage for linked coupling faults, inclusive of undetectable faults identified by the single-pass march test.

Introduction and objective: The aim of the study is to summarize the knowledge about hypothyroidism, with particular emphasis on Hashimoto's disease, as its most common cause. Review metods: Literature review of PubMed database using key words contained in ‘Medical Subject Headings’ MeSH. State of Knowledge: Hashimoto's disease is the most common form of thyroiditis, as well as main cause of hypothyroidism. It is an autoimmune disease that leads to gradual fibrosis and atrophy of the thyroid gland. It occurs several times more frequently in women than in men. Treatment mainly involves supplementation of thyroid hormones due to the progressive hypothyroidism. Levothyroxine (L-T4) therapy has a long history of clinical use, a defined pharmacological profile, and is considered as safe treatment of hypothyroidism of the thyroid gland. There are also other, less common causes of hypothyroidism, such as postoperative hypothyroidism, de Quervain's disease, post-radioactive iodine treatment status, drug-induced and central hypothyroidism, which are equally important and should not be forgotten during the diagnostic process. Summary: Hypothyroidism can be caused by various factors, the main being Hashimoto’s thyroiditis. Regardless of the etiology, treatment in most cases involves levothyroxine (LT-4) supplementation, which leads to euthyroidism and resolution of symptoms. Surgery may need to be performed in pateitns who meet the surgical criteria and show unresponsiveness to conservative treatment.

Introduction and Purpose: Human health is influenced by a variety of factors, such as genetics, environment, lifestyle, and accessibility to healthcare. While some of these factors are beyond the control of the patient, lifestyle, which is considered the primary determinant of a healthy life, strongly relies on individual choices. In this paper, we aim to demonstrate the benefits of adopting a vegetarian diet as a cornerstone for maintaining good health and as a supplementary approach to treating common diseases.State of Knowledge: The vegetarian diet is primarily based on plants and includes products from animals, such as eggs and dairy. However, it excludes all types of meat and any products that require the death of animals. This diet is adopted for various reasons, including religious, socio-economic, or ethical considerations. It is recognized globally and has become a subject of scientific research for numerous scholars. Many studies investigate its influence on human health, and the results are generally positive. The diet is frequently used as a treatment, often in combination with specific pharmaceutical drugs. This approach leads to weight reduction, decreases the risk of cardiovascular diseases, and can have positive therapeutic effects on conditions like gout or chronic kidney disease. Given that some of these diseases have become increasingly problematic for public health systems, a vegetarian diet can help decrease the number of people affected by them.Conclusion: Given that cardiovascular diseases and incidents are the leading causes of death worldwide, adopting a vegetarian diet can assist patients in avoiding them by reducing their LDL levels and decreasing blood pressure. This diet demonstrates a positive therapeutic effect on patients dealing with chronic kidney disease and gout. It aids in weight reduction and helps prevent the development of metabolic syndrome, which has a variety of beneficial effects.

Introduction and Purpose: Tennis elbow and golfer's elbow are two stress syndromes of the elbow joint region which have received much attention due to their effects on everyday and sporting activities. This review intends to provide an up-to-date summary of the pathophysiology, clinical manifestation, diagnostic techniques, and treatment options for the two conditions. State of Knowledge: Recent research has emphasized the complexity of these diseases, connecting various causes to their emergence. The current study also shows how inflammation, tendon degradation, and neural involvement contribute to these disorders. Imaging advancements, such as ultrasound and MRI, have improved the diagnostic process by allowing visualization and recognition of underlying disorders. To ensure proper management, differential diagnoses, such as nerve compression syndromes and other musculoskeletal diseases, must be carefully evaluated. Rest, physiotherapy, NSAIDs, and corticosteroid injections are important first-line treatments. Novel therapeutic interventions, such as PRP therapy and ESWT have recently been studied as supplements or alternatives to traditional procedures. The exercise-based rehabilitation in controlling and preventing recurrence is also emphasized. Although surgery is reserved for the most difficult cases, advances in minimally invasive techniques have resulted in better outcomes. Conclusion: Recent literature has significantly contributed to our understanding of elbow stress syndromes. The synthesis of recent research provides clinicians with valuable insights into optimal management strategies. Although, further research is crucial to improve diagnosis, develop new treatments, and raise the standard of care for those affected by these conditions.

Introduction and purpose: The aim of this study is to to review and analyze scientific research on the topic of clavicle fractures, including epidemiology and comparison of the current conservative and surgical treatment options. State of Knowledge: Due to its structure and function as a support for the upper limb, the clavicle is one of the most frequently fractured bones in the human body. Any significant force acting on the shoulder, such as direct trauma or a fall onto an outstretched hand, can result in high stress forces, leading to a clavicle fracture. Depending on the location of the fracture, muscles pull the bone fragments in their respective directions, which affects the treatment approach for each type of fracture.To facilitate the choice of treatment method, classifications such as the Neer classification and the Edinburgh classification have been developed. Various surgical techniques as well as conservative treatments have been employed in the management of clavicle fractures. Conclusions: The epidemiology of clavicle fractures shows a higher incidence in young males, particularly related to sports activities. The majority of fractures occur in the middle third of the clavicle, with fractures in the distal and proximal thirds being less common. Understanding the ligamentous connections of the clavicle is crucial for understanding fracture patterns. There is no single preferred method of treatment, therefore both conservative and surgical methods are used in the therapeutic process depending on the fracture type. The functional outcome of various surgical techniques is similar.